Notes

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This review discusses the preparation and therapeutic strategies describing in vitro and in vivo experiments using graphene-based materials in the context of PNI and their ability to promote nerve tissue regeneration.Treatments promoting post-stroke functional recovery continue to be an unmet therapeutic problem with physical rehabilitation being the most reproduced intervention in preclinical and clinical studies. Unfortunately, physiotherapy is typically effective at high intensity and early after stroke - requirements that are hardly attainable by stroke survivors. The aim of this study was to directly evaluate and compare the dose-dependent effect of delayed physical rehabilitation (daily 5 h or overnight voluntary wheel running; initiated on post-stroke day 7 and continuing through day 21) on recovery of motor function in the mouse photothrombotic model of ischemic stroke and correlate it with angiogenic potential of the brain. Our observations indicate that overnight but not 5 h access to running wheels facilitates recovery of motor function in mice in grid-walking test. Western blotting and immunofluorescence microscopy experiments evaluating the expression of angiogenesis-associated proteins VEGFR2, doppel and PDGFRβ in the peri-infarct and corresponding contralateral motor cortices indicate substantial upregulation of these proteins (≥2-fold) in the infarct core and surrounding cerebral cortex in the overnight running mice on post-stroke day 21. These findings indicate that there is a dose-dependent relationship between the extent of voluntary exercise, motor recovery and expression of angiogenesis-associated proteins in this expert-recommended mouse ischemic stroke model. Notably, our observations also point out to enhanced angiogenesis and presence of pericytes within the infarct core region during the chronic phase of stroke, suggesting a potential contribution of this tissue area in the mechanisms governing post-stroke functional recovery.
Artificial intelligence advances have stimulated a new generation of autosegmentation, however clinical evaluations of these algorithms are lacking. This study assesses the clinical utility of deep learning-based autosegmentation for MR-based prostate radiotherapy planning.

Data was collected prospectively for patients undergoing prostate-only radiation at our institution from June to December 2019. Geometric indices (volumetric Dice-Sørensen Coefficient, VDSC; surface Dice-Sørensen Coefficient, SDSC; added path length, APL) compared automated to final contours. Physicians reported contouring time and rated autocontours on 3-point protocol deviation scales. Descriptive statistics and univariable analyses evaluated relationships between the aforementioned metrics.

Among 173 patients, 85% received SBRT. The CTV was available for 167 (97%) with median VDSC, SDSC, and APL for CTV (prostate and SV) 0.89 (IQR 0.83-0.95), 0.91 (IQR 0.75-0.96), and 1801mm (IQR 1140-2703), respectively. Physicians completed survforts are needed to educate and generate consensus among physicians, and develop mechanisms to flag cases for quality assurance.
In preclinical radio-oncological research, local tumour control is considered the most relevant endpoint as it reflects the inactivation of cancer stem cells. Preclinical tumour-control assays may compare dose-response curves between different radiotherapy strategies, e.g., assessing additional targeted drugs and immunotherapeutic interventions, or between different radiation modalities. To mimic the biological heterogeneity of human tumour populations and to accommodate for approaches of personalized oncology, preclinical studies are increasingly performed combining larger panels of tumour models. For designing the study protocols and to obtain reliable results, prospective sample-size planning has to be developed that accounts for such heterogeneous cohorts.

A Monte-Carlo-based method was developed to estimate the sample size of a comparative 11 two-arm prospective tumour-control assay. Based on repeated logistic regression analysis, pre-defined dose levels, assumptions on the dose-response curves of thoach in the experimental arm. The software is publicly available and can be applied to plan comparisons of sigmoidal dose-response curves based on logistic regression.
An approach for estimating the required animal number for comparative tumour-control assays in a heterogeneous population is presented, allowing also the inclusion of different treatments as a personalized approach in the experimental arm. The software is publicly available and can be applied to plan comparisons of sigmoidal dose-response curves based on logistic regression.
Prophylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC) patients improves survival. However, it is also associated with cognitive impairment, although the underlying mechanisms remain poorly understood. Selleck LY2109761 Our study aims to evaluate the impact of PCI and potential benefit of hippocampal sparing (HS) on brain metabolism assessed by
F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography (
F-FDG PET/CT).

We retrospectively included 22 SCLC patients. 50% had hippocampal-sparing (HS) PCI.
F-FDG PET/CT was performed 144.5±73days before and 383±451days after PCI. Brain
F-FDG PET scans were automatically segmented in 12 regions using Combined-AAL Atlas from MI-Neurology Software (Syngo.Via, Siemens Healthineers). For all atlas regions, we computed SUV Ratio using brainstem as a reference region (SUVR=SUVmean/Brainstem SUVmean) and compared SUVR before and after PCI, using a Wilcoxon test, with a level of significance of p<0.05.

We found significant decreases in
F-FDG brain metabolism after PCI in the basal ganglia (p=0.004), central regions (p=0.001), cingulate cortex (p<0.001), corpus striata (p=0.003), frontal cortex (p<0.001), parietal cortex (p=0.001), the occipital cortex (p=0.002), precuneus (p=0.001), lateral temporal cortex (p=0.001) and cerebellum (p<0.001). Conversely, there were no significant changes in the mesial temporal cortex (MTC) which includes the hippocampi (p=0.089). The subgroup who received standard PCI showed a significant decrease in metabolism of the hippocampi (p=0.033). Contrastingly, the subgroup of patients who underwent HS-PCI showed no significant variation in metabolism of the hippocampi (p=0.783).

PCI induced a diffuse decrease in
F-FDG brain metabolism. HS-PCI preserves metabolic activity of the hippocampi.
PCI induced a diffuse decrease in 18F-FDG brain metabolism. HS-PCI preserves metabolic activity of the hippocampi.
Neutrophil-to-lymphocyte ratio has been correlated with clinical outcomes in many cancers. We investigated whether the delta-NLR (ΔNLR) following radiation therapy (RT) could predict achieving surgical resection and the overall survival (OS) of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC), and whether the splenic radiation dose impacted ΔNLR.

101 patients with biopsy-proven BRPC or LAPC who received induction chemotherapy followed by RT were retrospectively enrolled. Following contouring of spleens, dose-volume histograms (DVHs) for splenic dosimetric parameters were calculated. Pre- and post-RT complete blood counts (CBC) within two weeks were recorded. Delta (Δ) values were calculated by subtracting the post-RT value from the pre-RT value. Cox regression survival analysis for pre and postradiation CBC values and OS was performed. Receiver operating curves (ROC) were generated and optimal cutoff points for highest sensitivity and specificity were identified. Ka chemotherapy, elevated ΔNLR after RT significantly predicts worse OS and decreased odds of achieving resection. Furthermore, ΔNLR is correlated with higher splenic doses, suggesting the spleen may be an important organ at risk.
Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC.

Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software.

In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p=0.013, 0.r validation.
This study was conducted to evaluate the longitudinal impact of postmastectomy radiation therapy (PMRT) on persistent severe lymphedema (PSL) using arm volume measurements by an infrared optoelectronic volumetry.

Of the patients who underwent mastectomy between 2008 and 2016, we included 330 patients with secondary arm lymphedema. Percentage of excessive volume (PEV) of the arm were serially assessed using an optoelectronic volumetry 1, 3, 6, 12, 18, 24, 36, and 48months after the lymphedema diagnosis (T
). We defined PSL as 2 or more episodes of PEV≥20%. Risk factors for PSL were evaluated using stepwise regression analyses.

Patients who received PMRT (n=202, 61.2%) were more likely to have larger extent of axillary node dissection (AND), and frequent stage II/III lymphedema at T
than those who did not receive PMRT (p<0.001). With a median follow-up of 72.5months, PSL occurred in 71 (21.5%) patients. Patients with PSL were more frequently treated with AND of≥20 nodes without reconstruction, had advanced lymphedema stage and higher PEV at T
, and more frequent events of cellulitis compared to those without PSL. The risk of developing PSL was significantly associated with PMRT with regional node irradiation (RNI), AND of ≥20 nodes, lymphedema stage, and PEV at T
, cellulitis, and compliance with physical therapy.

PMRT, especially RNI, was associated with a consistent increase in PEV in patients with arm lymphedema. Therefore, timely physical therapy is necessary for this patient population.
PMRT, especially RNI, was associated with a consistent increase in PEV in patients with arm lymphedema. Therefore, timely physical therapy is necessary for this patient population.
Local treatment of metastases in combination with systemic therapy can prolong survival of oligo-metastasized patients. To fully exploit this potential, safe and effective treatments are needed to ensure long-term metastases control. Stereotactic body radiotherapy (SBRT) is one means, however, for moving liver tumors correct delivery of high doses is challenging. After validating equal in-vivo treatment accuracy, we analyzed a pooled multi-platform liver-SBRT-database for clinical outcome.

Local control (LC), progression-free interval (PFI), overall survival (OS), predictive factors and toxicity was evaluated in 135 patients with 227 metastases treated by gantry-based SBRT (deep-inspiratory breath-hold-gating; n=71) and robotic-based SBRT (fiducial-tracking, n=156) with mean gross tumor volume biological effective dose (GTV-BED
) of 146.6Gy
.

One-, and five-year LC was 90% and 68.7%, respectively. On multivariate analysis, LC was significantly predicted by colorectal histology (p=0.006). Median OS was 20months with one- and two-year OS of 67% and 37%.
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